Objectives of these studies are to analyze the molecular mechanisms underlying specific stage transitions in multistage carcinogenesis, comparing the mechanisms of promoting agents with those of carcinogens, singly or in combinations. Receptors for tumor promoting phorbol esters (e.g., TPA) were characterized in normal and malignant human hematopoietic cells. Presently these molecules are being isolated from human platelet membranes. b) Enhancement of hexose transport and the presence of receptors for epidermal growth factor (EGF) have been studied for their role in the mitogenic effect of phorbol esters on postinitiated mouse epidermal cell lines. Clonal variants which undergo a mitogenic response to TPA enhance their hexose uptake rate in response to phorbol esters and possess EGF receptors while mitogenically unresponsive variants lack both the hexose uptake response and EGF receptors. Mitogenic effects of tumor promotors, which are likely to mediate early stages of preneoplastic progression in vivo, appear to depend on enhancement of hexose uptake and of EGF receptors. c) Alterations in several protein kinase activities associated with malignant transformation will be studied in epithelial cells through different stages of preneoplastic progression.